I can reproduce, but as soon as I switch to a layout tab it re-enables. Are there situations it never enables?
If you open a project and the first tab is an event sheet, it's not clear what layout should run when you press Run Layout (for example, the event sheet could be included by 5 other event sheets, so which is its associated layout?). So C2 waits until you switch to a layout tab to know that's the layout you want to run. You can always right-click and run in the project bar, too.